Year
Month
(Peer-Reviewed) Design, synthesis, and evaluation of fluoroquinolone derivatives as MicroRNA-21 small-molecule inhibitors
Yuan-Yuan Hei 黑媛媛 ¹ ³, Si Wang ² ³, Xiao-Xiao Xi 席肖肖 ¹, Hai-Peng Wang 王海鹏 ⁴, Yuanxu Guo ² ³, Minhang Xin 辛敏行 ¹ ³, Congshan Jiang 蒋丛姗 ² ³, Shemin Lu 吕社民 ² ³, San-Qi Zhang 张三奇 ¹ ³
¹ Department of Medicinal Chemistry, School of Pharmacy, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China
中国 西安 西安交通大学医学部药学院药物化学系
² Institute of Molecular and Translational Medicine (IMTM), and Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China
中国 西安 西安交通大学医学部基础医学院 转化医学研究院 生物化学与分子生物学系
³ Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an, 710061, China
中国 西安 环境与疾病相关基因教育部重点实验室(西安交通大学)
⁴ Department of Medical Oncology, Shaanxi Provincial People's Hospital, Xi'an, 710068, China
中国 西安 陕西省人民医院肿瘤内科
Abstract

MicroRNA-21 (miRNA-21) is highly expressed in various tumors. Small-molecule inhibition of miRNA-21 is considered to be an attractive novel cancer therapeutic strategy. In this study, fluoroquinolone derivatives A1–A43 were synthesized and used as miRNA-21 inhibitors.

Compound A36 showed the most potent inhibitory activity and specificity for miRNA-21 in a dual-luciferase reporter assay in HeLa cells. Compound A36 significantly reduced the expression of mature miRNA-21 and increased the protein expression of miRNA-21 target genes, including programmed cell death protein 4 and phosphatase and tensin homology deleted on chromosome ten, at 10 μM in HeLa cells. The Cell Counting Kit-8 assay was used to evaluate the antiproliferative activity of A36; the results showed that the IC50 value range of A36 against six tumor cell lines was between 1.76 and 13.0 μM. Meanwhile, A36 did not display cytotoxicity in BEAS-2B cells (lung epithelial cells from a healthy human donor).

Furthermore, A36 significantly induced apoptosis, arrested cells at the G0/G1 phase, and inhibited cell-colony formation in HeLa cells. In addition, mRNA deep sequencing showed that treatment with A36 could generate 171 dysregulated mRNAs in HeLa cells, while the expression of miRNA-21 target gene dual-specificity phosphatase 5 was significantly upregulated at both the mRNA and protein levels. Collectively, these findings demonstrated that A36 is a novel miRNA-21 inhibitor.
Design, synthesis, and evaluation of fluoroquinolone derivatives as MicroRNA-21 small-molecule inhibitors_1
Design, synthesis, and evaluation of fluoroquinolone derivatives as MicroRNA-21 small-molecule inhibitors_2
Design, synthesis, and evaluation of fluoroquinolone derivatives as MicroRNA-21 small-molecule inhibitors_3
Design, synthesis, and evaluation of fluoroquinolone derivatives as MicroRNA-21 small-molecule inhibitors_4
  • Power grid fault diagnosis based on a deep pyramid convolutional neural network
  • Xu Zhang 张旭, Huiting Zhang, Dongying Zhang, Yixian Wang, Ruiting Ding, Yuchuan Zheng, Yongxu Zhang
  • CSEE Journal of Power and Energy Systems
  • 2022-05-06
  • China's factor reallocation effect considering energy
  • Guangqing Xu, Xiaoyu Chen
  • Chinese Journal of Population, Resources and Environment
  • 2022-05-02
  • Cannabidiol prevents depressive-like behaviors through the modulation of neural stem cell differentiation
  • Ming Hou, Suji Wang, Dandan Yu, Xinyi Lu, Xiansen Zhao, Zhangpeng Chen, Chao Yan
  • Frontiers of Medicine
  • 2022-04-26
  • Cultivation of gut microorganisms of the marine ascidian Halocynthia roretzi reveals their potential roles in the environmental adaptation of their host
  • Yang Yang, Yuting Zhu, Haiming Liu, Jiankai Wei, Haiyan Yu, Bo Dong
  • Marine Life Science & Technology
  • 2022-04-26
  • Data network traffic analysis and optimization strategy of real-time power grid dynamic monitoring system for wide-frequency measurements
  • Jinsong Li, Hao Liu, Wenzhuo Li, Tianshu Bi, Mingyang Zhao
  • Global Energy Interconnection
  • 2022-04-25
  • Field distribution of the Z₂ topological edge state revealed by cathodoluminescence nanoscopy
  • Xiao He, Donglin Liu, Hongfei Wang, Liheng Zheng, Bo Xu, Biye Xie, Meiling Jiang, Zhixin Liu, Jin Zhang, Minghui Lu, Zheyu Fang
  • Opto-Electronic Advances
  • 2022-04-25
  • Advances in femtosecond laser direct writing of fiber Bragg gratings in multicore fibers: technology, sensor and laser applications
  • Alexey Wolf, Alexander Dostovalov, Kirill Bronnikov, Mikhail Skvortsov, Stefan Wabnitz, Sergey Babin
  • Opto-Electronic Advances
  • 2022-04-25
  • Graphene-empowered dynamic metasurfaces and metadevices
  • Chao Zeng, Hua Lu, Dong Mao, Yueqing Du, He Hua, Wei Zhao, Jianlin Zhao
  • Opto-Electronic Advances
  • 2022-04-25
  • Charge carrier dynamics in different crystal phases of CH₃NH₃PbI₃ perovskite
  • Efthymis Serpetzoglou, Ioannis Konidakis, George Kourmoulakis, Ioanna Demeridou, Konstantinos Chatzimanolis, Christos Zervos, George Kioseoglou, Emmanuel Kymakis, Emmanuel Stratakis
  • Opto-Electronic Science
  • 2022-04-21
  • Applications of optically and electrically driven nanoscale bowtie antennas
  • Zhongjun Jiang, Yingjian Liu, Liang Wang
  • Opto-Electronic Science
  • 2022-04-20
  • Validation of the bodily expressive action stimulus test among Chinese adults and children
  • Yunmei Yang, Wenwen Hou, Jing Li
  • PsyCh Journal
  • 2022-04-17



  • Large-area straight, regular periodic surface structures produced on fused silica by the interference of two femtosecond laser beams through cylindrical lens                                Semen microbiota in normal and leukocytospermic males
    About
    |
    Contact
    |
    Copyright © PubCard